Publications by authors named "Qihong Yan"

Mucosal antigen-specific T cells are pivotal for pathogen clearance and immune modulation in respiratory infections. Dysregulated T cell responses exacerbate coronavirus disease 2019 severity, marked by cytokine storms and respiratory failure. Despite extensive description in peripheral blood, the characteristics of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific T cells in the lungs remain elusive.

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Background: Although immunoglobulin (Ig) alleles play a pivotal role in the antibody response to pathogens, research to understand their role in the humoral immune response is still limited.

Methods: We retrieved the germline sequences for the IGHV from the IMGT database to illustrate the amino acid polymorphism present within germline sequences of IGHV genes. We aassembled the sequences of IgM and IgD repertoire from 130 people to investigate the genetic variations in the population.

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Research on virus/receptor interactions has uncovered various mechanisms of antibody-mediated neutralization against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, understanding of neutralization by antibodies targeting the silent face, which recognize epitopes on glycan shields, remains limited, and their potential protective efficacy in vivo is not well understood. This study describes a silent face neutralizing antibody, 3711, which targets a non-supersite on the N-terminal domain (NTD) of the spike protein.

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The COVID-19 pandemic has underscored vaccination as a crucial strategy for reducing disease severity and preventing hospitalizations. Heterologous boosters using aerosolized Ad5-nCoV following two doses of inactivated vaccine have demonstrated superior antibody responses. However, the comprehensive dynamics of this antibody boost and the optimal timing for heterologous boosters are still not fully understood.

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Article Synopsis
  • - Continued evolution of SARS-CoV-2 leads to new variants that evade immunity from infections and vaccinations, raising concerns about how these variants develop in populations with varying immunity levels.
  • - Researchers identified a specific group of neutralizing antibodies (VL6-57) that effectively target certain regions of the virus's spike protein, with similarities seen regardless of their heavy chain variations.
  • - The study shows that certain mutations in the Omicron variant allow it to escape recognition by these VL6-57 antibodies, suggesting that these antibodies could be driving the virus's evolution in response to population immunity.
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  • Scientists studied a special part of the coronavirus called the spike protein, which changes over time and affects how our bodies fight the virus with antibodies.
  • They found an antibody called D1F6 that works really well against many new versions of the virus, including a recent one called XBB.1.5.
  • Some changes in the virus's spike protein can make it harder for D1F6 to work, but several changes together can block it much better, showing how the virus can avoid being attacked by our immune defenses.
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  • The emergence of Omicron subvariants challenges the effectiveness of current vaccines and therapeutic antibodies, leading to increased breakthrough infections linked to weak mucosal IgA responses from mRNA vaccines.
  • Researchers engineered new forms of IgA antibodies that showed significantly improved neutralizing abilities against various Omicron lineages compared to traditional IgG antibodies.
  • Administering these enhanced IgA antibodies nasally could offer a promising strategy for both preventing and treating Omicron infections, addressing issues of immune evasion by newer variants.
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Omicron, as the emerging variant with enhanced vaccine tolerance, has sharply disrupted most therapeutic antibodies. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) belongs to the subgenus Sarbecovirus, members of which share high sequence similarity. Herein, we report one sarbecovirus antibody, 5817, which has broad-spectrum neutralization capacity against SARS-CoV-2 variants of concern (VOCs) and SARS-CoV, as well as related bat and pangolin viruses.

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Article Synopsis
  • Researchers are developing a new vaccine to protect against multiple betacoronaviruses, including SARS-CoV-2 variants and MERS-CoV, due to their significant public health threat.
  • The vaccine uses a mosaic ferritin nanoparticle that displays key spike proteins from different coronaviruses, showing strong immune responses and efficacy in mice and nonhuman primates.
  • Administering a low dose at intervals results in effective protection against various β-CoVs, suggesting this vaccine may serve as a broad-spectrum option for future outbreaks.
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  • Neutralizing antibodies play a crucial role in protecting against SARS-CoV-2, but current methods can't track specific antibodies in the immune response.
  • Researchers developed an antibodyomics pipeline that combines high-throughput sequencing and analysis to identify and map spike-specific neutralizing antibodies and their lineages.
  • The study found that while many antibodies can target various epitope sites on the spike protein, only a few persist long-term, suggesting a need for more effective vaccine designs based on these findings.
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SARS-CoV-2 spike protein (S) is structurally dynamic and has been observed by cryo-EM to adopt a variety of prefusion conformations that can be categorized as locked, closed, and open. S-trimers adopting locked conformations are tightly packed featuring structural elements incompatible with RBD in the "up" position. For SARS-CoV-2 S, it has been shown that the locked conformations are transient under neutral pH.

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SARS-CoV-2 Omicron variants feature highly mutated spike proteins with extraordinary abilities in evading antibodies isolated earlier in the pandemic. Investigation of memory B cells from patients primarily with breakthrough infections with the Delta variant enables isolation of a number of neutralizing antibodies cross-reactive to heterologous variants of concern (VOCs) including Omicron variants (BA.1-BA.

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SARS-CoV-2 variants continue to emerge facing established herd immunity. L452R, previously featured in the Delta variant, quickly emerged in Omicron subvariants, including BA.4/BA.

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Population antibody response is thought to be important in selection of virus variants. We report that SARS-CoV-2 infection elicits a population immune response that is mediated by a lineage of VH1-69 germline antibodies. A representative antibody R1-32 from this lineage was isolated.

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The identification of a novel class of shark-derived single domain antibodies, named vnarbodies that show picomolar affinities binding to the receptor binding domain (RBD) of Wuhan and Alpha, Beta, Kappa, Delta, Delta-plus, and Lambda variants, is reported. Vnarbody 20G6 and 17F6 have broad neutralizing activities against all these SARS-CoV-2 viruses as well as other sarbecoviruses, including Pangolin coronavirus and Bat coronavirus. Intranasal administration of 20G6 effectively protects mice from the challenges of SARS-CoV-2 Wuhan and Beta variants.

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COVID-19 is an immune-mediated inflammatory disease caused by SARS-CoV-2 infection, the combination of anti-inflammatory and antiviral therapy is predicted to provide clinical benefits. We recently demonstrated that mast cells (MCs) are an essential mediator of SARS-CoV-2-initiated hyperinflammation. We also showed that spike protein-induced MC degranulation initiates alveolar epithelial inflammation for barrier disruption and suggested an off-label use of antihistamines as MC stabilizers to block degranulation and consequently suppress inflammation and prevent lung injury.

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HIV-1 latency posts a major obstacle for HIV-1 eradication. Currently, no desirable latency reversing agents (LRAs) have been implicated in the "Shock and Kill" strategy to mobilize the latently infected cells to be susceptible for clearance by immune responses. Identification of key cellular pathways that modulate HIV-1 latency helps to develop efficient LRAs.

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SARS-CoV-2 infection-induced hyper-inflammation links to the acute lung injury and COVID-19 severity. Identifying the primary mediators that initiate the uncontrolled hypercytokinemia is essential for treatments. Mast cells (MCs) are strategically located at the mucosa and beneficially or detrimentally regulate immune inflammations.

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Article Synopsis
  • The study investigated the B cell response to SARS-CoV-2 by analyzing the mRNA transcripts of antibody heavy chains from 24 blood samples of 10 COVID-19 patients over time.
  • It found significant clonal expansion of naive B cells with low somatic hypermutation around the second week after infection, correlating with increased levels of spike-specific IgG antibodies.
  • Additionally, the research identified similarities between the IgH repertoire of patients and known monoclonal antibodies, indicating a convergent and robust immune response to the virus.
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Recent studies have highlighted observations regarding re-tested positivity (RP) of SARS-CoV-2 RNA in discharged COVID-19 patients, however, the immune mechanisms underlying SARS-CoV-2 RNA RP in immunocompetent patients remain elusive. Herein, we describe the case of an immunocompetent COVID-19 patient with moderate symptoms who was twice re-tested as positive for SARS-CoV-2 RNA, and the period between first and third viral RNA positivity was 95 days, longer than previously reported (18-25 days). The chest computed tomography findings, plasma anti-SARS-CoV-2 antibody, neutralizing antibodies (NAbs) titer, and whole blood transcriptic characteristics in the viral RNA RP patient and other COVID-19 patients were analyzed.

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Monoclonal antibodies (mAbs) encoded by IGHV3-53 (VH3-53) targeting the spike receptor-binding domain (RBD) have been isolated from different COVID-19 patients. However, the existence and prevalence of shared VH3-53-encoded antibodies in the antibody repertoires is not clear. Using antibody repertoire sequencing, we found that the usage of VH3-53 increased after SARS-CoV-2 infection.

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Coronavirus disease 2019 (COVID-19) is caused by a novel coronavirus named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), with some patients developing severe illness or even death. Disease severity has been associated with increased levels of proinflammatory cytokines and lymphopenia. To elucidate the atlas of peripheral immune response and pathways that might lead to immunopathology during COVID-19 disease course, we performed a peripheral blood RNA sequencing analysis of the same patient's samples collected from symptom onset to full recovery.

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Article Synopsis
  • Zika virus infection during pregnancy can lead to serious congenital defects, including fetal microcephaly, and monoclonal antibodies (MAbs) targeting the nonstructural protein 1 (NS1) offer a potential way to mitigate this risk without worsening the disease.
  • Two specific MAbs, 3G2 and 4B8, have been found to effectively inhibit Zika virus infection in neonatal mice through different mechanisms, utilizing both antibody-dependent cell-mediated cytotoxicity (ADCC) and other pathways that don’t involve Fcγ receptors.
  • The study highlights the importance of the specific regions of the NS1 protein that the MAbs target, indicating that an MAb's protective capabilities may depend on its epito
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